With understanding the action principle of a temperature-sensitive hydrogel, numerous application and development have been reported. For example, a polymer mixture composed of Pluronic F-127 exhibiting a temperature-induced phase transition and sodium hyaluronate controlling viscosity maintained its liquid state at room temperature and solidified at the time of delivery into the body through injection. Thereby being stabilized in a wound has been suggested [Korean Unexamined Patent Application Publication No. 2007-0100701; Patent Document 1] and an investigation example using a copolymer of Pluronic F-127 and sodium hyaluronate as a delivery system for an anti-cancer agent has been suggested [Chem Pharm Bull 57(5) 453-458 (2009); Non-Patent Document 1]. Recently, the inventors reported a nanoparticle/hydrogel composite (exenatide-loaded Pluronic F-68 nanoparticles with F-127) and a blood sugar regulatory effect was demonstrated for three days or longer with one administration [European Journal of Pharmaceutics and Biopharmaceutics 88, 664-669 (2014); Non-Patent Document 2].
However, because the above-mentioned drug delivery systems are dependent on the concentration of the polymer of the delivery system, they are easily solubilized (or disintegrated) when administered so that a fast drug release state due to instability is exhibited. Particularly, when a water-soluble drug or protein drug and antibodies are contained, due to excellent solubility in an aqueous solution, fast drug release is induced, and thus it is difficult to realize the desired efficacy. To overcome these difficulties, repeated administration of a drug is required and an increase in treatment cost is expected in the case of an expensive protein drug or antibody. As alternatives as presented in Patent Document 1, a combination of a temperature-sensitive polymer and various types of drug-loaded nanoparticles was used, but remarkable improvement in efficacy was not achieved with the composite material of a polymer and nanoparticles.
Accordingly, there is a demand for a novel type of temperature-sensitive composite which has increased stability in the body, maintains excellent redispersibility in an aqueous solution when prepared in the form of powder, and exhibits sustained drug efficacy by controlling a drug release rate.